CTRI/2025/02/081078 [Registered on: 21/02/2025] Trial Registered Prospectively
Last Modified On:
06/04/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
A study to test whether exposure to BI 690517 in combination with empagliflozin helps people participants with heart failure
Scientific Title of Study
A Phase III double-blind randomized parallel-group superiority trial to evaluate efficacy and safety of the combined use of oral BI 690517 and empagliflozin compared with placebo and empagliflozin in participants with symptomatic heart failure (HF: NYHA II-IV) and left ventricular ejection fraction (LVEF) more than equals to 40 percent.
Argentina Australia Belgium Brazil Bulgaria Canada Chile China Colombia Czech Republic Germany Hungary India Italy Japan Mexico Netherlands Poland Republic of Korea Romania Saudi Arabia Serbia Slovenia South Africa Spain Taiwan Turkey United Kingdom United States of America Viet Nam
ndhra Medical College, Maharanipeta, Visakhapatnam-530002 Visakhapatnam ANDHRA PRADESH
7075852341
drjennymadhuriresearch@gmail.com
Dr Jabir Abdullakutty
Lisie Hospital
P.B No. 3053 Ernakulam KERALA
9447011773
drjabi@yahoo.co.in
Dr Vijay Kumar Chopra
Max Super Speciality Hospital
East Block- A unit of Devki Devi Foundation, 2, Press Enclave road 110017 South DELHI
9650896800
Vijay.chopra@maxhealthcare.com
Dr Sanjay Mittal
Medanta The Medicity
Sector 38, Gurugram- 122001 Gurgaon HARYANA
9910044477
sanjay.mittal@medanta.org
Dr Srikanth KV
Narayana Institute of Cardiac Sciences
(A unit of Narayana Hrudayalaya Limited), NH Health City, 258/A, Bommasandra Industrial Area, Anekal Taluk, Bangalore - 560099, Karnataka, India Bangalore KARNATAKA
9342659468
srikanth.kv.dr01@narayanahealth.org
Dr Dinesh Choudhary
S.P. Medical College and A G of Hospitals
Bikaner - 334001, Rajasthan, India Bikaner RAJASTHAN
9414222727
drdineshchoudhary8@gmail.com
Dr Cecily Mary Majella
Tamil Nadu Government Multi Super Specialty Hospital
Omandurar Estate, Chennai - 600002, TamilNadu, India Chennai TAMIL NADU
9443584151
drceilym.research@gmail.com
Dr Devangkumar Maheshchandra Desai
Unicare Heart Institute and Research Center
Acme Plaza, B- Wing, Near Sosyo Circle, B/H New Civil Hospital, Canal Road,395002 Surat GUJARAT
Dose: 1 tablet once daily
Route: oral
Duration: 148 weeks
Comparator Agent
Empagliflozin
Dose: 1 tablet once daily
Route: oral
Duration: 148 weeks
Comparator Agent
Placebo matching BI 690517
Dose: 1 tablet once daily
Route: oral
Duration: 148 weeks
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Eligible participants will have a diagnosis of HF with LVEF 40 percent and meet eligibility criteria below.
1. At least 18 years old and at least of the legal age of consent in countries where it is greater than 18 years
2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
3. Male or female participants. Women of childbearing potential1 must be ready and able to use highly effective methods of birth control per International Conference on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1percent per year when used consistently and correctly. A list of contraception methods meeting these criteria and instructions on the duration of their use is provided in the participant information.
4. Chronic HF diagnosed at least 3 months before Visit 1, and in NYHA class II-IV at Visit 1, with LVEF 40 percent per local reading (obtained by echocardiography, radionuclide ventriculography, invasive angiography, MRI, or CT). A historical LVEF may be used if it was measured within 12 months prior to Visit 1, or the LVEF may be measured after study consent has been obtained and before Visit 2 (if several values are available, the most recent one should be considered)
5. Presence of structural heart abnormality (confirmed by any imaging modality; i.e. echocardiography at Visit 1, as defined by left ventricular hypertrophy or left atrial enlargement) (see Appendix 10.3). Historical imaging may be used if performed within 12 months prior to Visit 1, or imaging may be completed after study consent has been obtained and before Visit 2. If several values are available, the most recent one should be considered.
6. At least one of the following: (a) Currently treated with diuretic therapy e.g. loop diuretics or thiazides, and on a stable dose for at least 1 week prior to Visit 1 (b) Documented hospitalisation for HF within 6 months prior to Visit 1 (c) Elevated NT-proBNP at Visit 1, analysed at the central laboratory at Visit 1 (a). in participants without Afib or Aflutter (at Visit 1 ECG): 900 pg/mL (b). for participants with Afib or Aflutter (at Visit 1 ECG): 1800 pg/mL
7. Participants must be treated according to best possible SOC in accordance with applicable HF local/international guidelines (according to the judgment of the investigator) Additional inclusion criteria apply to the optional accelerometry substudy: (1) Willing and able to provide informed consent for substudy participation; and (2) Capable of ambulation, with or without a walking aid.
8. Elevated NTproBNP at Visit 1, analysed at the central laboratory at Visit 1 a) n participants with BMI less than 27 kg/m2 more than equals to 300 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and more than equals to 900 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG), (b) in participants with BMI more than equals to 27 kg/m2 to less than 35 kg/m2 more than equals to 220 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and more than equals to 660 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG) (c) in participants with BMI more than equals to 35 kg/m2 more than equals to 125 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and more than equals to 375 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG)
ExclusionCriteria
Details
1. Treatment with an MRA (e.g. spironolactone, eplerenone, finerenone) within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator. Treatment with MRA should not be interrupted with the intention of enrolment into the study
2. Treatment with amiloride, or other potassium-sparing diuretic within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator
3. Receiving the following treatments:
a. a direct renin inhibitor (e.g. aliskiren) at Visit 2
b. more than one ACEI, ARB or ARNI, or two simultaneously at Visit 2
c. Acute decompensated HF requiring hospitalisation or i.v. therapy including diuretics, or i.v. inotropes or i.v. vasodilators, mechanical support (such as an intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, any ventricular assist device), or IV natriuretic peptide (e.g. nesiritide) within the past 7 days prior to Visit 2
4. MI, CVA, TIA, stroke, coronary artery bypass graft surgery/CABG, heart valve surgery or any other major surgery (major according to the investigator assessment) within 90 days prior to Visit 1, or scheduled for major elective surgery (e.g. hip replacement, coronary artery bypass graft surgery/CABG)
5. Heart transplant recipient, awaiting heart transplant, or currently implanted LVAD
6. Known cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, hypertrophic obstructive cardiomyopathy or known pericardial constriction, or cardiomyopathy with potentially reversible cause such as stress or peripartum cardiomyopathy or cardiomyopathy induced by chemotherapy within the 12 months prior to Visit 1 and until Visit 2
7. Acute inflammatory heart disease, such as acute myocarditis, within the 90 days preceding prior to Visit 1and until Visit 2
8. Known severe valvular heart disease (obstructive or regurgitant), as per investigator judgment, or valvular heart disease scheduled for surgical or invasive procedures at Visit 1, or anticipated invasive treatment during the study
9. Atrial fibrillation or Atrial flutter with a resting heart rate more than 110 bpm documented by ECG at Visit 1
10. Untreated clinically relevant ventricular arrhythmia without an ICD at Visit 1 and/or Visit 2
11. Unless managed with an implanted pacemaker: symptomatic bradycardia, sick sinus syndrome, Mobitz Type II second degree AV-Block, or third-degree heart block
12. Implantation of ICD or CRT within 3 months prior to Visit 1 or until Visit 2
13. Symptomatic hypotension and/or a SBP less than 100 mmHg at Visit 1 or Visit 2
14. SBP more than equals to 180 mmHg at Visit 1 or Visit 2. If SBP more than 150 mmHg and less than 180 mmHg at Visit 1, the participant should be receiving at least 3 antihypertensive drugs.
15. Severe chronic pulmonary disease according to investigators judgment: e.g. with known FEV1 less than 50 percent or need for home oxygen, primary pulmonary arterial hypertension, or chronic obstructive pulmonary disease exacerbation requiring i.v. or chronic oral steroids within 3 months prior to Visit 1 or until Visit 2
16. Serum potassium more than 5.2 mmol/L measured by the central laboratory at Visit 1 (Note one reassessment of serum potassium is allowed during screening)
17. ALT or AST more than 3x ULN at Visit 1 or known hepatic cirrhosis (Child Pugh C), or other liver disease causing severe impaired liver function, according to investigators judgment
18. Impaired renal function, defined as eGFR less than 20 mL/min/1.73 m2 (CKD-EPI) as determined at Visit 1 by the central laboratory, or on renal replacement therapy. (Note: one reassessment of eGFR is allowed during screening)
19. Haemoglobin (Hb) less than 9 g/dL as determined at Visit 1 by the central laboratory
20. Known adrenal insufficiency (e.g. Addison disease) or Cushing syndrome
21. History of ketoacidosis within 5 years prior to Visit 1 or until Visit 2
22. Gastrointestinal surgery or gastrointestinal disorder that could interfere with trial medication absorption in the investigators opinion
23. Type 1 diabetes mellitus, or history of other autoimmune causes of diabetes mellitus (e.g. LADA)
24. Any documented active or suspected malignancy or history of malignancy within 5 years prior to Visit 1, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix or low risk prostate cancer (participants with pre treatment PSA less than 10 ng/mL and biopsy Gleason score of more than equals to 6 and clinical stage T1c or T2a)
25. Presence of any other disease than heart failure with a life expectancy of less than 1 year in the investigators opinion
26. Participants who must or wish to continue the intake of restricted medications (see Section 4.2.2.1) or any drug considered likely to interfere with the safe conduct of the trial
27. Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other
investigational treatment(s). Those participating in a purely observational trial will not be excluded.
28. Chronic alcohol or drug abuse or any condition that, in the investigators opinion, makes them an unreliable trial participant or unlikely to complete the trial
29. Women who are pregnant, nursing, or who plan to become pregnant while in the trial
30. Intolerance or known allergy or hypersensitivity to BI 690517 or empagliflozin or other SGLT2 inhibitors and/or any of the excipients (including lactose). A list of BI 690517 and empagliflozin and placebo ingredients is provided in the ISF.
31. Any condition not covered by any of the other exclusion criteria, including abnormal laboratory values, which in the investigators opinion, might jeopardise the participants safety or compliance with the protocol
Method of Generating Random Sequence
Other
Method of Concealment
Other
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To demonstrate the superiority of the combination of BI 690517 10 mg and empagliflozin 10 mg compared with placebo and empagliflozin 10 mg for the time to first CV death or HHF in participants with HF and LVEF more than equals to 40%, based on a hazard ratio
Time to first event of CV death or HHF. Death and HHF will be categorised by the investigator according to pre-specified criteria
Secondary Outcome
Outcome
TimePoints
to demonstrate the superiority of the combination of BI 690517
10 mg & empagliflozin 10 mg to placebo & empagliflozin 10 mg for the time to first event of CV death, HHF or urgent HF visit, the total number of HHF (first & recurrent), the absolute change from baseline in KCCQ-TSS at Week 32 [R17-2666], the time to CV death & the time to all-cause mortality
Time to first event of CV death, HHF or urgent heart failure visit
Occurrences of HHFs (first & recurrent)
Absolute change from baseline in KCCQ-TSS at Week 32
Time to CV death
Time to all-cause mortality
Target Sample Size
Total Sample Size="6000" Sample Size from India="150" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
31/03/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
08/07/2024
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="2" Months="8" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This trial is a double-blind, randomised, parallel-group,
multi-centre, Phase III clinical trial investigating the combined use of oral
BI 690517 and empagliflozin compared with placebo and empagliflozin in
participants with symptomatic HF and LVEF ≥40%.
The treatment period duration will be based on accrual of
primary endpoint events.
Participants, investigators, and everyone involved in trial
conduct or analysis, or with any other interest in this double-blind trial,
will remain blinded with regard to the randomised treatment assignments until
after database lock. Emergency unblinding will be available to the investigator
via the IRT.
Overall sample size: approx. 6000*
Sample size for each
group (n = 2 groups): approx. 3000 participants per group